tbuckley/cabot-search huggingface dataset:
Dupilumab sustains efficacy in patients with moderate‐to‐severe type 2 asthma regardless of inhaled corticosteroids dose
Authors: Ian D. Pavord, Arnaud Bourdin, Alberto Papi, Christian Domingo, Jonathan Corren, Arman Altincatal, Amr Radwan, Nami Pandit‐Abid, Juby A. Jacob‐Nara, Yamo Deniz, Paul J. Rowe, Elizabeth Laws, David J. Lederer, Megan Hardin
Journal: Allergy (2023)

Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins-4/13, key and central drivers of type 2 inflammation. The TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who completed a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Here, we assess whether dupilumab sustains long-term efficacy in patients regardless of inhaled corticosteroid (ICS) dose at parent study baseline (PSBL).Patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose ICS at PSBL and enrolled in TRAVERSE were included. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1 ), 5-item asthma control questionnaire, and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO.Of patients with type 2 asthma (n = 1666), 891 (53.5%) were receiving high-dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab versus placebo were 0.517 versus 1.883 (phase 2b) and 0.571 versus 1.300 (QUEST) over the parent study (52 weeks) and remained low throughout TRAVERSE (0.313-0.494). Improvements in pre-BD FEV1 were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups.Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS.
Recent progress of micro/nanomotors to overcome physiological barriers in the gastrointestinal tract
Authors: Shuhao Zhang, Chaoran Zhu, Wanting Huang, Hua Liu, Mingzhu Yang, Xuejiao Zeng, Zhenzhong Zhang, Junjie Liu, Jinjin Shi, Yurong Hu, Xiufang Shi, Zhi-Hao Wang
Journal: Journal of Controlled Release (2023)
Intrapartum Azithromycin vs Placebo for Neonatal Sepsis—Reply
Authors: Anna Roca, Bully Camara, Halidou Tinto
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cytisinicline for Smoking Cessation
Authors: Nancy A. Rigotti, Neal L. Benowitz, Judith Prochaska, Scott Leischow, Mitchell Nides, Brent Blumenstein, Anthony Clarke, Daniel Cain, Cindy Jacobs
Journal: JAMA (2023)

Importance Cytisinicline (cytisine) is a plant-based alkaloid that, like varenicline, binds selectively to α4β2 nicotinic acetylcholine receptors, which mediate nicotine dependence. Although not licensed in the US, cytisinicline is used in some European countries to aid smoking cessation, but its traditional dosing regimen and treatment duration may not be optimal. Objective To evaluate the efficacy and tolerability of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs placebo. Design, Setting, and Participants A 3-group, double-blind, placebo-controlled, randomized trial (ORCA-2) compared 2 durations of cytisinicline treatment (6 or 12 weeks) vs placebo, with follow-up to 24 weeks, among 810 adults who smoked cigarettes daily and wanted to quit. It was conducted at 17 US sites from October 2020 to December 2021. Interventions Participants were randomized (1:1:1) to cytisinicline, 3 mg, 3 times daily for 12 weeks (n = 270); cytisinicline, 3 mg, 3 times daily for 6 weeks then placebo 3 times daily for 6 weeks (n = 269); or placebo 3 times daily for 12 weeks (n = 271). All participants received behavioral support. Main Outcomes and Measures Biochemically verified continuous smoking abstinence for the last 4 weeks of cytisinicline treatment vs placebo (primary) and from end of treatment to 24 weeks (secondary). Results Of 810 randomized participants (mean age, 52.5 years; 54.6% female; mean of 19.4 cigarettes smoked daily), 618 (76.3%) completed the trial. For the 6-week course of cytisinicline vs placebo, continuous abstinence rates were 25.3% vs 4.4% during weeks 3 to 6 (odds ratio [OR], 8.0 [95% CI, 3.9-16.3]; P &amp;amp;lt; .001) and 8.9% vs 2.6% during weeks 3 to 24 (OR, 3.7 [95% CI, 1.5-10.2]; P = .002). For the 12-week course of cytisinicline vs placebo, continuous abstinence rates were 32.6% vs 7.0% for weeks 9 to 12 (OR, 6.3 [95% CI, 3.7-11.6]; P &amp;amp;lt; .001) and 21.1% vs 4.8% during weeks 9 to 24 (OR, 5.3 [95% CI, 2.8-11.1]; P &amp;amp;lt; .001). Nausea, abnormal dreams, and insomnia occurred in less than 10% of each group. Sixteen participants (2.9%) discontinued cytisinicline due to an adverse event. No drug-related serious adverse events occurred. Conclusions and Relevance Both 6- and 12-week cytisinicline schedules, with behavioral support, demonstrated smoking cessation efficacy and excellent tolerability, offering new nicotine dependence treatment options. Trial Registration ClinicalTrials.gov Identifier: NCT04576949
Illness Denial in Medical Disorders: A Systematic Review
Authors: Chiara Patierno, Giovanni A. Fava, Danilo Carrozzino
Journal: Psychotherapy and Psychosomatics (2023)

Introduction: Illness denial pertains to medical patients who do not acknowledge the presence or severity of their disease or the need of treatment. Objective: This systematic review was performed to clarify the clinical role and manifestations of illness denial, its impact on health attitudes and behavior, as well as on short- and long-term outcomes in patients with medical disorders. Methods: The systematic search according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines was conducted on PubMed, Scopus, and Web of Science. Results: The initial search yielded a total of 14,098 articles; 176 studies met the criteria for inclusion. Illness denial appeared to be a relatively common condition affecting a wide spectrum of health attitudes and behavior. In some cases, it may help a person cope with various stages of illness and treatment. In other situations, it may determine delay in seeking treatment, impaired adherence, and reduced self-management, leading to adverse outcomes. The Diagnostic Criteria for Psychosomatic Research (DCPR) were found to set a useful severity threshold for the condition. An important clinical distinction can also be made based on the DCPR for illness denial, which require the assessment of whether the patient has been provided with an adequate appraisal of the medical situation. Conclusions: This systematic review indicates that patients with medical disorders experience and express illness denial in many forms and with varying degrees of severity. The findings suggest the need for a multidimensional assessment and provide challenging insights into the management of medical disorders.
Association of Racial Discrimination With Adiposity in Children and Adolescents
Authors: Adolfo G. Cuevas, Danielle M. Krobath, Brennan Rhodes-Bratton, Shu Xu, Jesulagbarami J. Omolade, Aniyah R. Perry, Natalie Slopen
Journal: JAMA Network Open (2023)

Childhood obesity is a major public health issue and is disproportionately prevalent among children from minority racial and ethnic groups. Personally mediated racism (commonly referred to as racial discrimination) is a known stressor that has been linked to higher body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) in adults, but little is known about the association of racial discrimination and childhood and adolescent adiposity.To assess the prospective association between self-reported experiences of racial discrimination and adiposity (BMI and waist circumference) in a large sample of children and adolescents in the Adolescent Brain Cognitive Development (ABCD) study.This cohort study used complete data from the ABCD study (2017 to 2019), involving a total of 6463 participants. The ABCD study recruited a diverse sample of youths from across the US, with rural, urban, and mountain regions. Data were analyzed from January 12 to May 17, 2023.The child-reported Perceived Discrimination Scale was used to quantify racial discrimination, reflecting participants' perceptions of being treated unfairly by others or unaccepted by society based on their race or ethnicity.Weight, height, and waist circumference were measured by trained research assistants. BMI z scores were computed by applying the US Centers for Disease Control and Prevention's age and sex-specific reference standards for children and adolescents. Waist circumference (inches) was quantified as the mean of 3 consecutive measures. Measurements were taken from time 1 (ie, 2017 to 2019) and time 2 (ie, 2018 to 2020).Of the 6463 respondents with complete data, 3090 (47.8%) were female, and the mean (SD) age was 9.95 (0.62) years. Greater racial discrimination exposure at time 1 was associated with higher BMI z score in both unadjusted (β, 0.05; 95% CI, 0.02-0.08) and adjusted regression models (β, 0.04; 95% CI, 0.01-0.08). Discrimination at time 1 was associated with higher waist circumference in unadjusted (β, 0.35; 95% CI, 0.15-0.54) and adjusted (β, 0.24; 95% CI, 0.04-0.44) models.In this cohort study of children and adolescents, racial discrimination was positively associated with adiposity, quantified by BMI z score and waist circumference. Interventions to reduce exposure to racial discrimination in early life may help reduce the risk of excess weight gain across throughout life.
Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study
Authors: Kyle C. White, Ary Serpa-Neto, Rod Hurford, Pierre Clement, Kevin B. Laupland, Emily See, James McCullough, Hayden White, Kiran Shekar, Alexis Tabah, Mahesh Ramanan, Peter Garrett, Antony G. Attokaran, Stephen Luke, Siva Senthuran, Philippa McIlroy, Rinaldo Bellomo, Mahesh Ramanan, Prashanti Marella, Patrick Young, Pip McIlroy, Ben Nash, James McCullough, Mandy Tallott, Andrea Marshall, David Moore, Hayden White, Sunil Sane, Lynette Morrison, Pam Dipplesman, Stephen Luke, Anni Paasilahti, Ray Asimus, Jennifer Taylor, Kyle White, David Cook, Peter Kruger, Jason Meyer, Rod Hurford., Kevin Plumpton, Andrew Barlow, Alexis Tabah, Hamish Pollock, Patrick Young, Antony G. Attokaran, Jacobus Poggenpoel, Josephine Reoch, Kevin B. Laupland, Felicity Edwards, Jayesh Dhanani, Marianne Kirrane, Pierre Clement, Nermin Karamujic, Paula Lister, Vikram Masurkar, Lauren Murray, Jane Brailsford, Todd Erbacher, Kiran Shekar, Jayshree Lavana, George Cornell, Siva Senthuran, Stephen Whebell, Gail Henson, Michelle Gatton, Zephanie Tyack, Robert Andrews, Arthur ter Hofstede, Moe Wynn, Kevin B. Laupland, Felicity Edwards
Journal: Intensive Care Medicine (2023)

The Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI.This is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition.Out of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1-1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32-0.36) for mortality.SA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria.
Tubular and Glomerular Size by Cortex Depth as Predictor of Progressive CKD after Radical Nephrectomy for Tumor
Authors: Aleksandar Denic, Mrunanjali Gaddam, Amr Moustafa, Aidan F. Mullan, Anthony C. Luehrs, Vidit Sharma, R. Houston Thompson, Maxwell L. Smith, Mariam P. Alexander, Lilach O. Lerman, Laura Barisoni, Andrew D. Rule
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Glomerular size differs by cortex depth. Larger nephrons are prognostic of progressive kidney disease, but it is unknown whether this risk differs by cortex depth or by glomeruli versus proximal or distal tubule size. We studied the average minor axis diameter in oval proximal and distal tubules separately and by cortex depth in patients who had radical nephrectomy to remove a tumor from 2019 to 2020. In adjusted analyses, larger glomerular volume in the middle and deep cortex predicted progressive kidney disease. Wider proximal tubular diameter did not predict progressive kidney disease independent of glomerular volume. Wider distal tubular diameter showed a gradient of strength of prediction of progressive kidney disease in the more superficial cortex than in the deep cortex. Background Larger nephrons are prognostic of progressive kidney disease, but whether this risk differs by nephron segments or by depth in the cortex is unclear. Methods We studied patients who underwent radical nephrectomy for a tumor between 2000 and 2019. Large wedge kidney sections were scanned into digital images. We estimated the diameters of proximal and distal tubules by the minor axis of oval tubular profiles and estimated glomerular volume with the Weibel–Gomez stereological model. Analyses were performed separately in the superficial, middle, and deep cortex. Cox proportional hazard models assessed the risk of progressive CKD (dialysis, kidney transplantation, sustained eGFR &lt;10 ml/min per 1.73 m 2 , or a sustained 40% decline from the postnephrectomy baseline eGFR) with glomerular volume or tubule diameters. At each cortical depth, models were unadjusted, adjusted for glomerular volume or tubular diameter, and further adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, postnephrectomy baseline eGFR, and proteinuria). Results Among 1367 patients were 62 progressive CKD events during a median follow-up of 4.5 years. Glomerular volume predicted CKD outcomes at all depths, but only in the middle and deep cortex after adjusted analyses. Proximal tubular diameter also predicted progressive CKD at any depth but not after adjusted analyses. Distal tubular diameter showed a gradient of more strongly predicting progressive CKD in the superficial than deep cortex, even in adjusted analysis. Conclusions Larger glomeruli are independent predictors of progressive CKD in the deeper cortex, whereas in the superficial cortex, wider distal tubular diameters are an independent predictor of progressive CKD.
Thirty-Five
Authors: Natalie Jabbar
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cytisinicline to Speed Smoking Cessation in the United States
Authors: Jonathan Foulds, Sophia I. Allen, Jessica Yingst
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Single-cell profiling reveals unique features of diabetogenic T cells in anti-PD-1-induced type 1 diabetes mice
Authors: Jenna L. Collier, Kristen E. Pauken, Catherine A.A. Lee, Dillon G. Patterson, Samuel C. Markson, Thomas S. Conway, Megan E. Fung, Joshua A. France, Kyla N. Mucciarone, Christine G. Lian, George F. Murphy, Arlene H. Sharpe
Journal: The Journal of Experimental Medicine (2023)

Immune-related adverse events (irAEs) are a notable complication of PD-1 cancer immunotherapy. A better understanding of how these iatrogenic diseases compare with naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced type 1 diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally exhausted/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3− T cells, and a decrease in memory CD4+FoxP3− and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ.
Pathogen‐Targeting Bimetallic Nanozymes as Ultrasonic‐Augmented ROS Generator against Multidrug Resistant Bacterial Infection
Authors: Hong Yao, Ruixue Zhou, Jiaming Wang, Yongbin Wei, Shihong Li, Zhenzhong Zhang, Xiang‐Dang Du, Sixuan Wu, Jinjin Shi
Journal: Advanced Healthcare Materials (2023)

Abstract Clinical treatment of multidrug resistant (MDR) pathogens‐induced infection is emerging as a growing challenge in global public health due to the limited selection of clinically available antibiotics. Nanozymes as artificial enzymes that mimicked natural enzyme‐like activities, are received great attention for combating MDR pathogens. However, the relatively deficient catalytic activity in the infectious microenvironment and inability to precisely targeting pathogen restrains their clinical anti‐MDR applications. Here, pathogen‐targeting bimetallic BiPt nanozymes for nanocatalytic therapy against MDR pathogen are reported. Benefiting from electronic coordination effect, BiPt nanozymes exhibit dual‐enzymatic activities, including peroxidase‐mimic and oxidase‐mimic activities. Moreover, the catalytic efficiency can be efficiently increased 300‐fold by ultrasound under inflammatory microenvironment. Notably, BiPt nanozyme is further cloaked with a platelet‐bacteria hybrid membrane (BiPt@HMVs), thus presenting excellent homing effect to infectious sites and precise homologous targeting to pathogen. By integrating accurate targeting with highly efficient catalytic, BiPt@HMVs can eliminate carbapenem‐resistant Enterobacterales and methicillin‐resistant Staphylococcus aureus in osteomyelitis rats model, muscle‐infected mice model, and pneumonia mice model. The work provides an alternative strategy based on nanozymes for clinically addressing MDR bacteria‐induced infections.
A Review of Glioblastoma and Other Primary Brain Malignancies
Authors: Alick P. Wang
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal